Enlargement of the prostate, which affects fifty percent of men aged 60 and ninety percent of men by age 85, is commonly referred to as benign prostate hyperplasia (BHP). BPH is a slow, progressive enlargement of the fibromuscular and epithelial structures of the prostate gland. The symptoms of BPH include decreased urinary flow, urinary retention, frequent urination and impotency. Substantial evidence indicates that the androgens testosterone and dihydrotestosterone (DHT) are contributing factors in producing BPH in the prostate. Tyler, V. E., The Honest Herbal: A sensible guide to the use of herbs and related remedies. (Pharmaceutical Products Press, New York 1982). Testosterone is converted by 5.alpha.-reductase to DHT which is about five times more potent than testosterone. DHT binds to cytoplasmic receptors in the prostate, where it initiates RNA and DNA synthesis. This action, in turn induces protein synthesis and abnormal growth of the prostate. (Tyler, V. E., Herbs of Choice: The therapeutic use of phytochemicals. (Pharmaceutical Products Press, New York 1994)). Current clinical evidence indicates that inhibition of 5.alpha.-reductase reverses the symptoms of BPH in human males. (Strauch, G. et al., Eur. Urol., Vol. 26, pp. 247-252 (1994); Rhodes, L. et al., Prostate, Vol. 22, pp. 43-51 (1993)).
There is now substantial evidence that androgen deprivation can decrease the obstructive symptoms of BPH. Further, 5.alpha.-reductase activity appears to be higher in cells obtained from BPH tissue than from normal prostate tissue. (Bone, K., The European Journal of Herbal Medicine, Vol. 4(1), pp. 15-24 (1998)). Inhibitors of 5.alpha.-reductase, such as the drug finasteride (PROSCAR), block the conversion of testosterone to DHT and have been found to reduce the size of the prostate leading to an increase in peak urinary flow rate and a reduction in symptoms (Strauch et al. 1994; Rhodes et al. 1993). Natural products such as the lipid extracts of Saw Palmetto berries (LESP), Serenoa repens, have also been found to reduce the conversion of testosterone to DHT by the inhibition of 5.alpha.-reductase both in vitro and in vivo (Bone, 1998; Di Silverio, F. et al., Eur. Urol., Vol. 21, pp. 309-314 (1992)).
Further, 5.alpha.-reductase has also been implicated as playing a central role in the proliferation of prostate cancer. Iehle, C. et al., Journal of Steroid Biochemistry and Molecular Biology, Vol. 54, pp. 273-279 (1995) (and references cited therein). See also, Isaacs, J. T. et al., J. Androl., Vol. 13 p. 457 (1992); Brinkmann, A. O. et al., J. Steroid Biochem. Mol. Biol., Vol. 41, p. 361 (1992); Simental, J. A. et al., J. Steroid Biochem. Mol. Biol., Vol. 43, p. 37 (1992); Ware, L. J. et al., Cancer Metastasis Rev., Vol. 12, p. 287 (1993); Steiner, M. S., Urology, Vol. 42, p. 99 (1993).
Astaxanthin, a red carotenoid has the following structure: ##STR1##
Haematococcus pluvialis microalgae is a natural source of astaxanthin. The microalgae also contains fatty acids such as palmitic, oleic, linoleic and stearic acids, protein, minerals, carbohydrates and vitamins. As explained more fully below, the present invention comprises the discovery that when tested in a 5.alpha.-reductase in vitro assay with a pre-digestion model, Haematococcus pluvialis algae meal containing the carotenoid astaxanthin demonstrated 98% inhibition of 5.alpha.-reductase at a concentration of 300 .mu.g/mL.
Thus, the major advantage provided by the present invention is a method of inhibiting the enzyme 5.alpha.-reductase in a human subject by the administration of a composition comprising the carotenoid astaxanthin. Because of its ability to inhibit the enzyme 5.alpha.-reductase, a composition comprising the carotenoid astaxanthin would therefore be useful for preventing and/or treating Benign Prostate Hyperplasia in a human subject, and preventing and/or treating prostate cancer in a human subject by administering a composition comprising astaxanthin to the subject.
These and additional objects and advantages of the present invention are shown from the description below. The disclosures of the publications cited above and throughout this specification are incorporated in their entirety to more fully describe the invention and to demonstrate the state of the art.